Leveraging ligand-based proton and electron transfer for aerobic reactivity and catalysis.

While O is an abundant, benign, and thermodynamically potent oxidant, it is also kinetically inert. This frequently limits its use in synthetic transformations. Correspondingly, direct aerobic reactivity with O often requires comparatively harsh or forcing conditions to overcome this kinetic barrier. Forcing conditions limit product selectivity and can lead to over oxidation. Alternatively, O can be activated by a catalyst to facilitate oxidative reactivity, and there are a variety of sophisticated examples where transition metal catalysts facilitate aerobic reactivity. Many efforts have focused on using metal-ligand cooperativity to facilitate the movement of protons and electrons for O activation. This approach is inspired by enzyme active sites, which frequently use the secondary sphere to facilitate both the activation of O and the oxidation of substrates. However, there has only recently been a focus on harnessing metal-ligand cooperativity for aerobic reactivity and, especially, catalysis. This perspective will discuss recent efforts to channel metal-ligand cooperativity for the activation of O, the generation and stabilization of reactive metal-oxygen intermediates, and oxidative reactivity and catalysis. While significant progress has been made in this area, there are still challenges to overcome and opportunities for the development of efficient catalysts which leverage this biomimetic strategy.